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991.
Xu XW Shi C He ZQ Ma CM Chen WH Shen YP Guo Q Shen CJ Xu J 《Cellular and molecular neurobiology》2008,28(6):875-886
The present study was undertaken to evaluate whether estrogen deprivation might lead to mitochondrial alteration of hippocampal
neurons of ovariectomized (OVX) rats, and to evaluate the protective effect of estrogen and phytoestrogen on the mitochondrial
alteration. First, OVX rats were used to mimic the pathologic changes of neurodegeneration of postmenopausal female, and we
looked into the alteration of the mitochondrial ultrastructure and ATP content of hippocampal CA1 region after ovariectomy
on different phase by transmission electron microscope (TEM) and reversed-phase high-performance liquid chromatography (HPLC),
and found the best phase points of the alteration of the mitochondrial ultrastructure and ATP content. Next, estrogen and
phytoestrogen were administered to the OVX rats for the protective effects on the mitochondrial ultrastructure and ATP content.
Meanwhile, the density, size, shape, and distribution parameters of mitochondrial ultrastructure were analyzed according to
the morphometry principle. The experimental results presented that (1) The alteration of mitochondrial ultrastructure elicited
by ovariectomy worsened with the days going on, and the changes were the most noteworthy in volume density (Vv), average surface
area (S), specific surface area (δ), and particle dispersity (Cλz) on 12th day (P < 0.05 or P < 0.01). Moreover, there was no statistical significance of the numerical density (Nv) among the five groups in the first
step experiment. (2) The treatment with estrogen, genistein (Gs), and ipriflavone (Ip) significantly reversed the effect elicited
by ovariectomy on Vv, S, δ, Cλz, Nv, and particle average diameter (D) of mitochondria of hippocampal CA1 region (P < 0.05). (3) Furthermore, ATP content of hippocampal CA1 region after ovariectomy declined significantly on 7th day (P < 0.05), and estrogen and phytoestrogen could reverse the alteration (P < 0.05). Taken together, these results revealed that phytoestrogen may have a protective role against the neurodegeneration
after menopause via protecting mitochondrial structure and functions. Phytoestrogen may be a good alternative as a novel therapeutic
strategy for menopausal syndrome. 相似文献
992.
Flamment M Arvier M Gallois Y Simard G Malthièry Y Ritz P Ducluzeau PH 《Biochimie》2008,90(9):1407-1413
The relationship between insulin resistance and mitochondrial function is of increasing interest. Studies looking for such interactions are usually made in muscle and only a few studies have been done in liver, which is known to be a crucial partner in whole body insulin action. Recent studies have revealed a similar mechanism to that of muscle for fat-induced insulin resistance in liver. However, the exact mechanism of lipid metabolites accumulation in liver leading to insulin resistance is far from being elucidated. One of the hypothetical mechanisms for liver steatosis development is an impairment of mitochondrial function. We examined mitochondrial function in fatty liver and insulin resistance state using isolated mitochondria from obese Zucker rats. We determined the relationship between ATP synthesis and oxygen consumption as well as the relationship between mitochondrial membrane potential and oxygen consumption. In order to evaluate the quantity of mitochondria and the oxidative capacity we measured citrate synthase and cytochrome c oxidase activities. Results showed that despite significant fatty liver and hyperinsulinemia, isolated liver mitochondria from obese Zucker rats display no difference in oxygen consumption, ATP synthesis, and membrane potential compared with lean Zucker rats. There was no difference in citrate synthase and cytochrome c oxidase activities between obese and lean Zucker rats in isolated mitochondria as well as in liver homogenate, indicating a similar relative amount of hepatic mitochondria and a similar oxidative capacity. Adiponectin, which is involved in bioenergetic homeostasis, was increased two-fold in obese Zucker rats despite insulin resistance. In conclusion, isolated liver mitochondria from lean and obese insulin-resistant Zucker rats showed strictly the same mitochondrial function. It remains to be elucidated whether adiponectin increase is involved in these results. 相似文献
993.
Vázquez-Memije ME Capin R Tolosa A El-Hafidi M 《Molecular and cellular biochemistry》2008,307(1-2):23-30
Throughout spermatogenesis, mitochondria undergo a morphological and functional differentiation. Mitochondria are involved
in the production of reactive oxygen species (ROS), considered one of the mediators of ageing. Particularly, lipid peroxidation
is regarded as a major phenomenon by which ROS can impair cellular function. In the present study, we examined the production
of superoxide anion, superoxide dismutase activity and the effect of Fe2+/ascorbate induced-lipid peroxidation on the respiratory chain activities of testis mitochondria throughout the process of
spermatogenesis and ageing. Mitochondria from rat testes generated superoxide anion, mainly using NADH as substrate, which
increased according to age. The activity of SOD is age-dependent and greatly stimulated during the first wave of spermatogenesis,
but decreases in adulthood and old age. TBARS concentration was also markedly increased by ageing. The activity of mitochondrial
respiratory chain complexes is differentially affected by oxidative stress induced by iron/ascorbate, succinate-dehydrogenase
activity being less vulnerable than that of NADH-dehydrogenase and cytochrome c oxidase. The data suggest that ageing is accompanied
by reduced activity of SOD, leading to excessive oxidative stress and enhanced lipid peroxidation that compromises the functionality
of the electron transport chain. The data support the concept that mitochondrial function is an important determinant in ageing. 相似文献
994.
Schapira AH 《Neurochemical research》2008,33(12):2502-2509
Mitochondria play a pivotal role in mammalian cell metabolism, hosting a number of important biochemical pathways including
oxidative phosphorylation. As might be expected from this fundamental contribution to cell function, abnormalities of mitochondrial
metabolism are a common cause of human disease. Primary mutations of mitochondrial DNA result in a diverse group of disorders
often collectively referred to as the mitochondrial encephalomyopathies. Perhaps more importantly in numerical terms are those
neurodegenerative diseases caused by mutations of nuclear genes encoding mitochondrial proteins. Finally there are mitochondrial
abnormalities induced by secondary events e.g. oxidative stress that may contribute to senescence, and environmental toxins
that may cause disease either alone or in combination with a genetic predisposition.
Special issue article in honor of Dr. Anna Maria Giuffrida-Stella. 相似文献
995.
Mitochondrial Complex I [NADH Coenzyme Q (CoQ) oxidoreductase] is the least understood of respiratory complexes. In this review
we emphasize some novel findings on this enzyme that are of relevance to the pathogenesis of neurodegenerative diseases. Besides
CoQ, also oxygen may be an electron acceptor from the enzyme, with generation of superoxide radical in the mitochondrial matrix.
The site of superoxide generation is debated: we present evidence based on the rational use of several inhibitors that the
one-electron donor to oxygen is an iron-sulphur cluster, presumably N2. On this assumption we present a novel mechanism of
electron transfer to the acceptor, CoQ. Complex I is deeply involved in pathological changes, including neurodegeneration.
Complex I changes are involved in common neurological diseases of the adult and old ages. Mitochondrial cytopathies due to
mutations of either nuclear or mitochondrial DNA may represent a useful model of neurodegeneration. In this review we discuss
Parkinson’s disease, where the pathogenic involvement of Complex I is better understood; the accumulated evidence on the mode
of action of Complex I inhibitors and their effect on oxygen radical generation is discussed in terms of the aetiology and
pathogenesis of the disease.
Special issue article in honor of Dr. Anna Maria Giuffrida-Stella. 相似文献
996.
Lasfer M Vadrot N Aoudjehane L Conti F Bringuier AF Feldmann G Reyl-Desmars F 《Cell biology and toxicology》2008,24(1):55-62
The heavy metal cadmium, an environmental pollutant, has been widely demonstrated to be toxic, in particular for liver. In
murines, cadmium induces apoptosis of hepatocytes and hepatomas. In human cells, apoptosis induced by cadmium has been exclusively
demonstrated in tumoral cell lines. Nothing was known in normal liver, in vitro or in vivo. In the present study, we examined the effects of cadmium in nonmalignant human hepatocytes. For that purpose, we investigated
whether cadmium was able to induce apoptosis of normal human hepatocytes (NHH) in primary culture and of a SV40-immortalized
human hepatocyte (IHH) cell line. Treatment of IHH and NHH with cadmium induced the presence of a sub-G1 population at 10 and 100 μmol/L, respectively. DAPI staining of both cell types treated with cadmium 100 μmol/L revealed
the induction of nuclear apoptotic bodies, supporting the hypothesis of apoptosis. In IHH and NHH, cadmium 100 μmol/L induced
PARP cleavage into a 85 kDa fragment. In order to investigate the involvement of mitochondria in cadmium-induced apoptosis,
we measured the mitochondrial membrane potential (ΔΨm). We observed that in IHH and NHH, cadmium 100 μmol/L induced a decrease of ΔΨm. As expected, cadmium under the same conditions enhanced caspase-9 and caspase-3 activities. In addition, cadmium from 1
to 100 μmol/L induced the expression of p53 and phosphorylation of its Ser15 in IHH and NHH. In conclusion, we showed in this
study that human hepatocytes were sensitive to cadmium and apoptosis induced at concentrations suggested in the literature
to inhibit p53 DNA-binding and DNA repair. 相似文献
997.
Foster DB Rucker JJ Marbán E 《Biochemical and biophysical research communications》2008,366(3):649-656
The subunit composition of the mitochondrial ATP-sensitive K+-channel (mitoKATP) is unknown, though some suspect a role for the inward rectifier, Kir6.1, based largely on antibody studies of heart mitochondria. To ascertain the molecular identity of mitoKATP we therefore sought to purify this putative mitochondrial Kir6.1, and conclusively identify the subunits by mass spectrometry. Immunoblots, conducted with two commercially available antibodies, revealed two distinct signals in isolated heart mitochondria, of 51 and 48 kDa, respectively. Localization was confirmed by either immuno-gold electron microscopy or by immunofluorescence. Each putative Kir6.1 species was extracted, purified, and identified by LC-MS/MS. The 51 kDa band was identified as NADH-dehydrogenase flavoprotein 1, while the preponderant protein in the 48-kDa band was mitochondrial isocitrate dehydrogenase (NADP form). 1D-, 2D-, and native gel analyses were consistent with these assignments. The data suggest it is premature to assign Kir6.1 a role in mitoKATP on the basis of immunoreactivity alone. 相似文献
998.
Sepsis impairs mitochondrial respiration but the mechanisms responsible are incompletely understood. We propose that Krebs cycle enzymes are inhibited in sepsis, contributing to reduced rates of oxidative phosphorylation. Hypothesis. The activities of Krebs cycle enzymes are decreased in endotoxemia and contribute to reduced rates of oxidative phosphorylation. Methods. Adult male rats received an intraperitoneal injection of either endotoxin or saline. Cardiac mitochondria were subsequently isolated and measures of mitochondrial respiration and enzyme activities performed. Main results. By 24 h post endotoxin administration, there was a 28% reduction in mitochondrial respiration (P = 0.0005) and a 24% reduction in aconitase activity (P = 0.001). Functional activity of the electron transport chain was unaffected. Conclusion. Our data demonstrate that in the heart, the administration of endotoxin significantly and selectively decreased aconitase activity in association with reduced rates of oxidative phosphorylation. We conclude that decreased activity of aconitase contributes to the endotoxin-stimulated reduction in mitochondrial respiration. 相似文献
999.
Pochini L Galluccio M Scumaci D Giangregorio N Tonazzi A Palmieri F Indiveri C 《Chemico-biological interactions》2008,173(3):187-194
The interaction of beta-lactams with the purified mitochondrial carnitine/acylcarnitine transporter reconstituted in liposomes has been studied. Cefonicid, cefazolin, cephalothin, ampicillin, piperacillin externally added to the proteoliposomes, inhibited the carnitine/carnitine antiport catalysed by the reconstituted transporter. The most effective inhibitors were cefonicid and ampicillin with IC50 of 6.8 and 7.6mM, respectively. The other inhibitors exhibited IC50 values above 36 mM. Kinetic analysis performed with cefonicid and ampicillin revealed that the inhibition is completely competitive, i.e., the inhibitors interact with the substrate binding site. The Ki of the transporter is 4.9 mM for cefonicid and 9.9 mM for ampicillin. Cefonicid inhibited the transporter also on its internal side. The IC50 was 12.9 mM indicating that the inhibition was less pronounced than on the external side. Ampicillin and the other inhibitors were much less effective on the internal side. The beta-lactams were not transported by the carnitine/acylcarnitine transporter. Cephalosporins, and at much lower extent penicillins, caused irreversible inhibition of the transporter after prolonged time of incubation. The most effective among the tested antibiotics was cefonicid with IC50 of 0.12 mM after 60 h of incubation. The possible in vivo implications of the interaction of the beta-lactam antibiotics with the transporter are discussed. 相似文献
1000.
Constitutively expressed HABP1 in normal murine fibroblast cell line induces growth perturbation, morphological abnormalities along with initiation of apoptosis. Here, we demonstrate that though HABP1 accumulation started in mitochondria from 48 hr of growth, induction of apoptosis with the release of cytochrome c and apoptosome complex formation occurred only after 60 hr. This mitochondrial dysfunction was due to gradual increase in ROS generation in HABP1 overexpressing cells. Along with ROS generation, increased Ca 2+ influx in mitochondria leading to drop in membrane potential was evident. Interestingly, upon expression of HABP1, the respiratory chain complex I was shown to be significantly inhibited. Electronmicrograph confirmed defective mitochondrial ultrastructure. The reduction in oxidant generation and drop in apoptotic cell population accomplished by disruption of HABP1 expression, corroborating the fact that excess ROS generation in HABP1 overexpressing cells leading to apoptosis was due to mitochondrial HABP1 accumulation. 相似文献